Method of cancer diagnosis using the analysis of isopopes

ABSTRACT

Disclosed is a method of diagnosing cancer on the basis of the quantitative analysis of blood or tissue isotopes. The method can accurately diagnose cancer even when it is too small for current conventional technology to diagnose.

TECHNICAL FIELD

The present invention relates, in general, to cancer diagnosis and, moreparticularly, to a method for diagnosing cancer on the basis ofquantitative analysis of isotopes of blood or tissue samples, which isable to accurately detect cancer even when it is too small to bedetected with conventional technologies.

BACKGROUND ART

Isotopes are any of several different forms of an element each having adifferent atomic mass (mass number). The term “isotope”, coined byBritish chemist F. Soddy in 1913, comes from the Greek isos“equal”+topos “place,” because despite the different atomic weights, thevarious forms of an element occupy the same place on the periodic table.

Generally, the chemical properties of an element depend on the number ofprotons, that is, the atomic number. Isotopes of an element have nucleihaving the same number of protons (the same atomic number) but differentnumbers of neutrons. Therefore, isotopes have different mass numbers,which indicate the total number of nucleons—the number of protons plusneutrons.

For example, oxygen occurs in nature as three different isotopes, eachwith 8 protons. The most common isotope is ¹⁶O (8 protons, 8 neutrons),which constitutes more than 99% of all oxygen atoms on earth. There isalso the rare isotope ¹⁸O (10 neutrons) and the even rarer isotope ¹⁷O(9 neutrons). Nitrogen exists as two stable isotopes, ¹⁴N and ¹⁵N, innature. Naturally occurring uranium is composed of three major isotopes,uranium-238, uranium-235, and uranium-234.

Because there are the same numbers of electrons as protons in anelement, isotopes of an element are identical in the number ofelectrons. Approximately 90 elements exist in nature, and there are asmany as about 300 naturally occurring isotopes, with an average of 3isotopes per element. In fact, tin (Sn) is the element with the greatestnumber of stable isotopes (ten), and cadmium has the second highestnumber of isotopes (eight) while there are elements that exist as onlyone isotope in nature, such as beryllium, fluorine, sodium and bismuth.

There is no general rule for relationship between a naturally occurringelement and the number of stable isotopes thereof. However, it has beenobserved that most of the elements that have odd atomic numbers eachhave two or fewer isotopes, whereas individual elements with even atomicnumbers have relatively many isotopes. A naturally occurring element isa mixture of isotopes with almost the same ratios therebetween orthereamong in any sample of the earth. In general, the atomic weight ofan element is the average of the atomic masses of all the chemicalelement's isotopes as found in a particular environment, weighted byisotopic abundance. The reason why a majority of atomic weights are notintegers or near-integers but decimals is that most elements areassemblages of isotopes. For a short-hand designation of differentisotopes (also called nuclides), the mass number (number of nucleons) iswritten in the right position or in the upper left corner of thechemical symbol, like oxygen-16, ¹⁶O, nitrogen-14 ¹⁴N, uranium-235 ²³⁵U,etc. Particularly as for hydrogen isotopes, specific names are giventhereto, such as protium for H-1, deuterium for H-2, and tritium forH-3.

Recent studies have showed that the oxygen isotope ¹⁸O is toxic toorganisms. Deuterium ²H in the form of D₂O was found to have 92%inhibitory activity against microorganisms and to kill rats at a rate of99.5% within 5 days.

High prevalence rates of cancer are reported in radioactivecontamination area, implying that persons excessively exposed toradioactive radiation may increase in isotope level in their bodies andmay be liable to affliction with cancer.

Leading to the present invention, intensive and thorough research intothe treatment and diagnosis of cancer, conducted by the presentinventor, resulted in the finding that cancer can be caused with achange in blood isotope level and that the incidence and kind of cancercan be diagnosed through the quantitative analysis of blood or tissueisotopes.

DISCLOSURE Technical Problem

The present invention pertains to cancer diagnosis through the analysisof blood or tissues for isotope content. It is difficult for evenup-to-date scientific technology to accurately diagnose tumors less than1 mm in size. However, blood analysis according to the present inventioncan provide a basis or criteria with which accurate diagnosis can beachieved for the incidence and kind of cancer in an early stage, thusgiving rise to an increase in the probability of successful cancertreatment. Therefore, it is an object of the present invention toprovide a method of diagnosing cancer by analyzing blood or tissueisotope levels and comparing them with those of normal persons.

Technical Solution

In order to accomplish the above object, the present invention providesa method of diagnosing cancer, comprising measuring levels of isotopesof an element in a blood sample or a tissue sample.

In accordance with a modification thereof, the element is selected froma group consisting of hydrogen, oxygen, magnesium, calcium, potassium,sulfur, chloride, silicon, iron, copper, and combinations thereof.

In accordance with another modification thereof, the method is based onan increase in the level of deuterium (²H) by 10% or higher compared toa normal standard.

In accordance with a further modification, the method is based on anincrease in the level of ¹⁸O by 10% or higher, compared to a normalstandard.

In accordance with still a further modification, the method is based onan increase in the level of a heavy isotope of the element compared to anormal standard.

In accordance with still another modification, the method is based onthe depletion of ⁴⁰K and/or ³⁶S from the sample.

Advantageous Effects

Featuring the quantitative analysis of blood or tissue isotopes, thepresent invention can accurately diagnose cancer even when it is toosmall for current conventional technology to diagnose. Hence, thepresent invention can make a great contribution to the treatment ofcancer and provide an opportunity for cancer patients to recover fromthe disease and lead a healthy life. It is well known that when canceris diagnosed in its early stage, it can be cured at a high success rate.However, diagnosis methods that can detect even small cancers withcertainty have not been developed yet. The present invention, whichovercomes the limitation of the prior art methods, can detect cancer inthe early stage thereof and thus allow cancer to be successfully cured.

BEST MODE

Prior to entry into the detailed description of the present invention,it should be noted that a description of well-known functions orconstitutions in conjunction with the present invention will be omittedin order to make the gist of the present invention unambiguous.

In the present invention, distilled water, mineral water, electrolysedwater, and blood and tissues from healthy persons and cancer patientsare qualitatively and quantitatively analyzed for isotopes. An exampleof an instrument for use in the isotope analysis includes EMAL-2 (EnergyMass Analyzer), which is a double-focus type mass spectrophotometer.Individual ions are used as laser sources for atomic ionization andvaporization.

A standard sample is used to correct the analysis results. In thisregard, 10 elements, including magnesium, silicon, sulfur, chloride,potassium, calcium, chrome, iron, copper, hydrogen, and oxygen, areemployed and analyzed for compositions in various samples. Stableisotopes analyzed in the present invention have mass numbers 24, 25 and26 for the element magnesium, mass numbers 28, 29 and 30 for the elementsilicon, mass numbers 32, 33, 34 and 36 for the element sulfur, massnumbers 35 and 37 for the element chloride, mass numbers 39, 40 and 41for the element potassium, mass numbers 40, 42, 43, 44, 46 and 48 forthe element calcium, mass numbers 50, 52, 53 and 54 for the elementchrome, mass numbers 54, 56, 57 and 58 for the element iron, and massnumbers 63 and 65 for the element copper. Prior to isotope analysis, allsamples except for water are dried at 360° C. for 1 hour in a vacuumoven.

SMOW (Standard Mean Ocean Water), which serves as a reference standardfor comparing hydrogen and oxygen isotope ratios, mostly in watersamples, is also used in the present invention. The isotope compositionof oxygen and hydrogen in a sample is expressed as per mil (% thousand)differences relative to SMOW. 4˜5 ml of water is reacted with uranium at800° C. in a vacuum of 10⁻⁵˜10⁻⁶ mmHg to generate hydrogen atoms for usein the measurement.

An instrument suitable for analyzing the isotope compositions ofhydrogen includes a Varian GD 150 isotope ratio mass spectrometer whilethe isotope compositions of oxygen in water and in gas phase samples areanalyzed using an Electron spectrometer (Sumi, Ukraine). Thesespectrometers can detect very small changes in the isotope compositionsof individual elements and analyze samples and a standardsimultaneously. The mass spectrometer is equipped with 2 or 3 ioncollectors and can measure 2˜3 ion currents at the same time and analyzethe relationship therebetween. The isotope compositions of elements inblood samples are analyzed using EMAL-2.

MODE FOR INVENTION

A better understanding of the present invention may be obtained throughthe following examples which are set forth to illustrate, but are not tobe construed as the limit of the present invention.

Example 1 Deuterium Level in Blood

Deuterium content was expressed as ppm relative to protium content.Listed in Table 1 are the numbers of ²D per 1,000,000 ¹H.

TABLE 1 Blood Samples D/H(in ppm) Normal 126 Stomach Cancer Patient 147Liver Cancer Patient 147.5 Lung Cancer Patient 148.2 Breast CancerPatient 147.6 Leukemia Patient 148.2

Cancer patients were measured to have a 15˜20% increase in the bloodlevel of deuterium, compared to normal persons.

Example 2 ¹⁸O Level in Blood

The oxygen isotope ¹⁸O content was expressed as ppm relative to theoxygen isotope ¹⁶O content. Listed in Table 1 are the numbers of ¹⁸O per1,000,000 ¹⁶O.

TABLE 2 Blood Samples ¹⁸O/¹⁶O(in ppm) Normal 1430 Stomach Cancer Patient1998 Liver Cancer Patient 1995 Lung Cancer Patient 1994 Breast CancerPatient 1996 Leukemia Patient 1995.5

Cancer patients were measured to have an about 35˜40% increase in theblood level of ¹⁸O, compared to normal persons.

Example 3 Comparison of Levels of Magnesium Isotopes in Blood

In Table 3, below, the measurements of blood magnesium isotope contentusing a mass spectrometer were expressed in arbitrary units.

TABLE 3 Blood Samples ²⁴M ²⁵M ²⁶M Normal 72.1 7.2 9.1 Stomach CancerPatient 69.5 9.5 23.2 Liver Cancer Patient 45.2 9.6 45.5 Lung CancerPatient 55.1 9.5 41.0 Breast Cancer Patient 55.6 15.2 33.2 LeukemiaPatient 40.2 8.5 52.6

The levels of heavy isotopes in the blood were measured to besignificantly increased in cancer patients, compared to normal persons.

Example 4 Comparison of Levels of Magnesium Isotopes in Blood

In Table 4, below, the measurements of blood silicon isotope contentusing a mass spectrometer are expressed in arbitrary units.

TABLE 4 Blood Samples ²⁸Si ²⁹Si ³⁰Si Normal 55.2 10.5 2.2 Stomach CancerPatient 65.3 25.7 8.6 Liver Cancer Patient 49.9 39.5 12.5 Lung CancerPatient 59.4 33.4 13.6 Breast Cancer Patient 65.8 30.2 8.6 LeukemiaPatient 65.3 25.6 10.5

The levels of heavy isotopes in the blood were measured to besignificantly increased in cancer patients, compared to normal persons.

Example 5 Comparison of Levels of Iron Isotopes in Blood

In Table 5, below, the measurements of blood iron isotope content usinga mass spectrometer are expressed in arbitrary units.

TABLE 5 Blood Samples ⁵⁴Fe ⁵⁶Fe ⁵⁷Fe ⁵⁸Fe Normal 3.2 58 14.1 2.1 StomachCancer Patient 3.6 68 25.1 3.3 Liver Cancer Patient 3.7 59 35.2 3.8 LungCancer Patient 4.1 63 28.5 3.5 Breast Cancer Patient 4.2 52 32.4 4.2Leukemia Patient 4.2 60.5 31.5 3.5

The levels of heavy isotopes in the blood were measured to besignificantly increased in cancer patients, compared to normal persons.

Example 6 Comparison of Levels of Copper Isotopes in Blood

In Table 6, below, the measurements of blood copper isotope contentusing a mass spectrometer are expressed in arbitrary units.

TABLE 6 Blood Samples ⁶³Cu ⁶⁵Cu Normal 65 35 Stomach Cancer Patient 7228 Liver Cancer Patient 63 41 Lung Cancer Patient 61 42 Breast CancerPatient 60 35 Leukemia Patient 74 25

There were no significant difference in light isotope levels betweencancer patients and normal persons.

Example 7 Comparison of Levels of Sulfur Isotopes in Blood

In Table 7, below, the measurements of blood sulfur isotope contentusing a mass spectrometer are expressed in arbitrary units.

TABLE 7 Blood Samples ³²S ³³S ³⁴S ³⁶S Normal 55.5 20.1 2.3 1.1 StomachCancer Patient 62.1 25.5 9.5 0 Liver Cancer Patient 52.1 35.5 12.3 0Lung Cancer Patient 58.9 26.5 13.2 0 Breast Cancer Patient 66.6 31.2 7.80 Leukemia Patient 61.2 25.9 10.3 0

The cancer patients were found to have a higher level of the heavyisotope than were normal persons. As for ³⁶S, however, it was notdetected in cancer patients, indicating that patients suffering fromcancer lack the isotope.

Example 8 Comparison of Levels of Chloride Isotopes in Blood

In Table 8, below, the measurements of blood chloride isotope contentusing a mass spectrometer are expressed in arbitrary units.

TABLE 8 Blood Samples ³⁵Cl ³⁷Cl Normal 60.2 25.3 Stomach Cancer Patient72.3 25.7 Liver Cancer Patient 71.5 28.8 Lung Cancer Patient 68.2 26.5Breast Cancer Patient 77.5 21.3 Leukemia Patient 63.2 32.1

The overall levels of heavy isotopes in the blood were observed to behigher in cancer patients compared to normal persons.

Example 9 Comparison of Levels of Potassium Isotopes in Blood

In Table 9, below, the measurements of blood potassium isotope contentusing a mass spectrometer were expressed in arbitrary units.

TABLE 9 Blood Samples ³⁹K ⁴⁰K ⁴¹K Normal 79.5 1.2 6.3 Stomach CancerPatient 86.4 0 10.5 Liver Cancer Patient 82.3 0 18.5 Lung Cancer Patient94.3 0 6.5 Breast Cancer Patient 77.5 0 16.2 Leukemia Patient 88.6 011.1

Of the potassium isotopes, ⁴⁰K was measured to be zero in cancerpatients, which distinguishes cancer patients from normal persons. Theheavy isotope was measured at higher levels in cancer patients than innormal patients.

Example 10 Comparison of Levels of Potassium Isotopes in Blood

In Table 10, below, the measurements of blood potassium isotope contentusing a mass spectrometer was expressed in arbitrary units.

TABLE 10 Blood Samples ⁴⁰Ca ⁴²Ca ⁴³Ca ⁴⁴Ca ⁴⁶Ca ⁴⁸Ca Normal 57.4 1.2 2.31.7 0.2 0.15 Stomach Cancer Patient 66.8 3.4 9.5 6.7 5.7 1.6 LiverCancer Patient 31.5 6.4 25.6 27.4 15.3 1.5 Lung Cancer Patient 54.2 4.618.7 17.5 7.6 1.2 Breast Cancer Patient 51.2 4.3 18.6 17.9 7.8 1.8Leukemia Patient 34.5 5.6 19.4 24.6 15.6 1.1

The heavy isotopes of element potassium were measured at higher levelsin cancer patients than in normal persons.

Taken together, the data obtained in the above examples demonstrate thatthe analysis of isotope levels in blood or tissues can be used todetermine the incidence of cancer, particularly based on an increase inisotope levels or the depletion of ⁴⁰K or ³⁶S.

Although the preferred embodiment(s) of the present invention have(has)been disclosed for illustrative purposes, those skilled in the art willappreciate that various modifications, additions and substitutions arepossible, without departing from the scope and spirit of the inventionas disclosed in the accompanying claims.

1. A method of diagnosing cancer, comprising measuring levels ofisotopes of an element in a blood sample or a tissue sample.
 2. Themethod according to claim 1, wherein the element is selected from agroup consisting of hydrogen, oxygen, magnesium, calcium, potassium,sulfur, chloride, silicon, iron, copper, and combinations thereof. 3.The method according to claim 1, wherein the method is based on anincrease in the level of deuterium (²H) by 10% or higher compared to anormal standard.
 4. The method according to claim 1, wherein the methodis based on an increase in the level of ¹⁸O by 10% or higher compared toa normal standard.
 5. The method according to claim 2, wherein themethod is based on an increase in the level of a heavy isotope of theelement compared to a normal standard.
 6. The method according to claim1, wherein the method is based on the depletion of ⁴⁰K and/or ³⁶S fromthe sample.